Surgical resection continues to be the only potentially curative treatment for PA. Recent evidence also demonstrates a survival advantage for adjuvant therapy after resection.7,8
Palliative chemotherapy and bypass surgery have been shown to be beneficial in improving the quality of life of selected patients with incurable disease.13
The present study uses a prospective population-based registry to capture patients at the time of diagnosis and consequently follow the management of their PA.
The OPCS was designed as a population-based registry of incident cases of PA in Ontario for epidemiologic, genetic and health services and outcomes research. Even with the use of E-path reporting and rapid case ascertainment, the overall response rate in the OPCS has never exceeded 35%, which is consistent with other attempts to obtain data through population-based registries of PA with the use of questionnaires.14
Despite the low response rate, we sought to characterize responders and nonresponders and use the OPCS to describe the management of PA in our registry of patients in Ontario. Our experience and observations underscore the need for further prospective, population-based studies of PA with emphasis on data collection from patients, physicians and existing administrative databases in the province. Our study simultaneously highlights the practical obstacles to progress, such as the rapid identification of patients with newly diagnosed PA.
We found that nonresponders were significantly older and more likely to have received treatment in a nonacademic centre than responders. This inverse relation between age and enrolment in prospective studies has been previously shown in cancer trials.15
Increasing age has been correlated with less aggressive management, which has been shown to be a barrier to participation in these studies owing to patient apathy and a sense of helplessness.16
Patients treated in nonacademic centres were less likely to respond to our recruitment strategy, possibly demonstrating the potential influence of an academic environment on the attitudes of these patients. In the province of Ontario, academic centres are geographically situated in the larger urban centres, and it has been shown that rural patients are less likely to participate in cancer research.16
However, it is also plausible that patients who are more likely to participate in research studies may be more likely to initially seek medical attention at an academic centre.
In our registry, patients aged 70 years and younger were more likely to undergo surgery with curative intent than those older than 70 years. Older patients are more likely to have medical comorbidities that would preclude surgery, and this was not accounted for in this study. However, the small number of patients unfit for the anesthetic or operative risk would likely not account for the statistical significance between these groups. Such a difference may be owing to physician education and attitudes toward aggressive surgical treatment in elderly patients and a tendency for physicians to be more aggressive in the treatment of younger patients.17
Other studies have also reported that older patients refuse pancreatic surgery more often than younger patients;18
however, this may be owing in part to the reluctance of surgeons to operate on older patients.
There is an ongoing trend toward centralization of management of PA in high-volume institutions owing to lower perioperative surgical morbidity and mortality.6,19,20
Our study examined the differences in the management of PA between academic and nonacademic centres and revealed that, within our registry, the number of aborted surgeries with curative intent was significantly higher in nonacademic centres than academic centres. However, when surgery with curative intent was completed, there was no significant difference in the percentage of positive margins between these 2 groups. This suggests that, although the decision to abort versus complete curative resection may have varied between academic and nonacademic centres, once the decision was made to complete a curative resection, surgical technique to acquire negative margins did not vary. This may indicate that a more aggressive approach to completion of surgery with curative intent is taken in academic centres with a higher threshold for aborting an operation with curative intent. However, it is also possible that the quality of preoperative staging evaluation and radiographic studies (e.g., pancreas protocol computed tomography, endoscopic ultrasonography) may be higher at academic centres; as a result, patients with technically unresectable disease may be identified preoperatively more often at academic centres, lowering the likelihood that an operative procedure would need to be aborted based on unexpected intraoperative findings.
All patients with stage-I or -II tumours for whom data was available underwent operations with curative intent, and all but 1 operation was completed. Bilimoria and colleagues18
found that 38.2% of their patients with stage-I or -II PA with no identifiable contraindication to surgery did not undergo surgical management. The likely difference in our database, in which all responders with stage-I or -II disease underwent surgical resection, is that our case ascertainment was limited to pathologic diagnosis and to questionnaire responders. As the usual management of clinically diagnosed early-stage PA is resection with no preoperative biopsy, the only pathology for these patients, which was our means of case ascertainment, was their surgical resection specimen. Owing to incomplete diagnosis of stage preoperatively, 36 (26%) patients with stage-III or -IV tumours had surgery with curative intent. There was no significant difference between the ability to diagnose unresectable tumours in academic compared with nonacademic centres. All surgeries with curative intent in patients with stage-III tumours were aborted in both academic and nonacademic centres, whereas the intraoperative decision to abort these surgeries in patients with stage-IV tumours was made more frequently in nonacademic centres than academic centres.
It has recently been shown that adjuvant chemotherapy should be offered to all patients with a diagnosis of PA.8
Although it is difficult to study the proportion of patients being offered chemotherapy, our analysis reveals that less than half of our patients received any adjuvant or palliative treatment, with no statistical differences demonstrated by either age or treatment site. This may be owing to our data collection having begun in 2003 before these guidelines were established. As stated, patient choice may also play a role; however, it is difficult to assess the proportion of patients being offered treatment and declining it. There was a significant difference in the use of chemotherapy based on stage of disease; patients undergoing curative surgical treatment for stage-I or -II tumours were less likely to receive chemotherapy as an adjunct to their treatment (13% and 40%, respectively) than those with stage-III or -IV tumours. Once again, this may be owing to both physician and patient knowledge and attitudes toward the role of chemotherapy.
Another finding in our study was the low enrolment in clinical trials across all patients, with no correlation between age or stage of disease and likelihood of enrolment. This may not be surprising, considering that most patients with cancer do not participate in clinical trials, and many patients with PA have poor performance status, limiting their eligibility for trials.
There are several limitations to our study. As PA is rapidly fatal, survival bias almost certainly affected our results. Although we used rapid case ascertainment to recruit patients, 44% of the patients died before enrolment. In addition, our response rate never exceeded 35%. Nonresponders may have had more aggressive disease and may have been less responsive to treatment. As a result, patients who underwent surgery may have been more eager to participate than patients with inoperable tumours. In fact, over 40% of our patients underwent surgery, which is double the number seen in the general PA population.2,3,11
Selection bias is also possible because we only recruited individuals with a pathologically confirmed diagnosis of PA. Over 50% (59% in 2002, Cancer Care Ontario: personal communication, 2006) of patients with PA in Ontario never have tissue confirmation while they are alive, and are only reported to the OCR from hospital records or death certificates.
Some patients may have been treated at more than 1 hospital and, although we used pathology reports and operative notes to classify the treatment centres, other decisions and treatment plans may have occurred elsewhere and were not accounted for in the analyses. Hospital records on chemotherapy were not always complete, although patient-acquired history was also used to determine use of chemotherapy. Of the 351 responders, only 269 had complete data from which to determine the stage of disease (i.e., in some patients a full work-up was not complete after diagnosis). Another limitation was the variation of synoptic pathology reporting, with different laboratories having varying thresholds for describing positive and negative margins.
Conclusions derived from the current data set must be interpreted in light of these limitations and may not be reflective of the entire population of patients with PA in Ontario. However, despite these limitations, to our knowledge this study provides the first overview of the management of PA in the province and the variables that may play a significant role in treatment strategies. Although the literature on current guidelines for the management of PA is quite thorough, very few studies examine the actual management strategies being used at a population level. We have demonstrated that even with rapid case ascertainment, response rates were low, and response rate was correlated with both age and treatment sites. We have also shown that age played a significant role in surgical management strategies and that treatment at an academic centre, although not significantly affecting margin status, correlated with rates of completed curative resections. The use of chemotherapy, either adjuvant or palliative, was low and varied depending on the stage of disease. This study has also demonstrated the need for further investigations into the epidemiologic limitations of collecting data in cancer populations with poor prognoses and the need to identify better methods to recruit patients shortly after diagnosis.